High frequency stimulation (HFS) is a promising method for the therapeutic control of epilepsy. Yet, the mechanisms for HFS mediated control of epilepsy are unknown. The ultimate goal of this research is to assist in the development of novel epilepsy therapies by investigating the mechanisms underlying the effect of HFS on neural tissue. Depolarization blockade, mediated through excess potassium in the extracellular space, has been postulated as one potential mechanism in HFS mediated control of epilepsy. Therefore, the overall objective of this proposal is to investigate relationship between HFS induced effects on neural tissue and potassium dynamics using multidisciplinary experimental approaches. Experiments will focus on the hippocampus as it is known for its' multiple, interrelated neural circuits as well as a foci for generation of epileptiform activity. Electrophysiology will be used to investigate the effects of HFS on neural tissue in vitro and in vivo, while patch clamping and ion-selective recording will explore underlying mechanisms for HFS mediated seizure control. A NEURON computer model will be developed to evaluate these mechanisms under conditions that would normally be difficult or impossible to test experimentally.